Zfhx3-mediated genetic ablation of the SCN abolishes light entrainable circadian activity while sparing food anticipatory activity

iScience

Patrick M. Nolan¹  Elizabeth Joynson¹  R. Sonia Bains¹  Ashleigh G. Wilcox¹  Debbie Williams¹  Lucie Vizor¹  Gareth Banks¹  Peter L. Oliver¹  Michael H. Hastings²  Elizabeth S. Maywood² 

[1] MRC Harwell Institute, Harwell Science Campus, Oxfordshire OX11 0RD, UK;MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK;

关键词: Biological sciences;    Physiology;    Molecular biology;    Neuroscience;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: Circadian rhythms persist in almost all organisms and are crucial for maintaining appropriate timing in physiology and behaviour. Here, we describe a mouse mutant where the central mammalian pacemaker, the suprachiasmatic nucleus (SCN), has been genetically ablated by conditional deletion of the transcription factor Zfhx3 in the developing hypothalamus. Mutants were arrhythmic over the light-dark cycle and in constant darkness. Moreover, rhythms of metabolic parameters were ablated in vivo although molecular oscillations in the liver maintained some rhythmicity. Despite disruptions to SCN cell identity and circuitry, mutants could still anticipate food availability, yet other zeitgebers - including social cues from cage-mates - were ineffective in restoring rhythmicity although activity levels in mutants were altered. This work highlights a critical role for Zfhx3 in the development of a functional SCN, while its genetic ablation further defines the contribution of SCN circuitry in orchestrating physiological and behavioral responses to environmental signals.

【 授权许可】

Unknown